PB0598 - Blood Anticoagulant Impacts Endogenous Thrombin Generation in a Peripartum Population

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

MB

Maria Cristina Bravo, PhD, PhD (she/her/hers)

Faculty Scientist
Department of Biochemistry, The Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT 05405, USA
Colchester, Vermont, United States

Co-Author(s)

IB

Ira Bernstein, MD

Professor and John van Sicklen Maeck Chair
Department of Obstetrics, Gynecology & Reproductive Sciences, The Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT 05405, USA
Burlington, Vermont, United States
MG

Matthew Gissel

Research Specialist
Department of Biochemistry, The Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT 05405, USA
Colchester, Vermont, United States
KM

Kelley McLean, MD

Associate Professor, Maternal Fetal Medicine
Department of Obstetrics, Gynecology & Reproductive Sciences, The Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT 05405, USA
Burlington, Vermont, United States
TO

Thomas Orfeo, PhD

Assistant Professor
Department of Biochemistry, The Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT 05405, USA
Colchester, Vermont, United States

Background: Plasmas from patients with pathologies associated with thrombotic risk have been reported to generate thrombin in the absence of exogenous initiator, with FXIa and microparticle-associated tissue factor (MP-TF) identified as potential initiators via the use of inhibitory antibodies. The peripartum period is associated with enhanced risk for thrombotic events but remains uncharacterized with respect to the presence of these initiators.

Aims: To characterize the frequency and origins of endogenous thrombin generation (ETG) in the peripartum period.

Methods: Healthy pregnant women (N=17) were prospectively enrolled in an IRB-approved study. Blood was collected via syringe at three visits: V1) 39-41 weeks of gestation; V2) 18-48 hours postpartum; V3) 4 months postpartum. Blood was anticoagulated into 3.2% sodium citrate (9:1, CIT) in the presence or absence of 0.1 mg/mL corn trypsin inhibitor (final concentration) (CTI, CTI/CIT) and platelet poor plasma prepared. Samples were thawed (CTI (0.1 mg/ml) added to CIT plasmas) and assayed for 1 hour on the Stago Thrombinoscope with MP (no exogenous TF) reagent in the presence or absence of an inhibitory anti-FXI/FXIa antibody.

Results: There were 16 out of 47 time points that showed no ETG in either anticoagulant (Table). In CIT plasma, all 31 of the remaining time points showed ETG that was partially or completely inhibited by the anti-FXI/FXIa antibody (Table). 24/31 time points with ETG in CIT showed no ETG in CTI/CIT.

Conclusion(s): In this peripartum population, blockade of FXII activation by CTI at the time of blood collection eliminates ~80% of the instances of ETG observed in matching samples anticoagulated with citrate alone. The data suggest these mechanisms: ETG observed in CTI/CIT plasma indicates the presence of MP-TF; FXIa observed in citrated plasma alone is generated post-phlebotomy, presumably reflecting the presence of material in the blood able to support contact pathway activation during plasma isolation.